Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia

S. H. Cass; J. W.D. Tobin; Y. D. Seo; G. Gener-Ricos; E. Z. Keung; E. M. Burton; M. A. Davies; J. L. McQuade; A. J. Lazar; R. Mason; M. Millward; S. Sandhu; C. Khoo; L. Warburton; V. Guerra; A. Haydon; H. Dearden; A. M. Menzies; M. S. Carlino; J. L. Smith; P. Mollee; M. Burgess; S. Mapp; C. Keane; V. Atkinson; S. A. Parikh; S. N. Markovic; W. Ding; T. G. Call; P. J. Hampel; G. V. Long; J. A. Wargo; A. Ferrajoli

doi:10.1016/j.annonc.2023.06.007

Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia

S. H. Cass, J. W.D. Tobin, Y. D. Seo, G. Gener-Ricos, E. Z. Keung, E. M. Burton, M. A. Davies, J. L. McQuade, A. J. Lazar, R. Mason, M. Millward, S. Sandhu, C. Khoo, L. Warburton, V. Guerra, A. Haydon, H. Dearden, A. M. Menzies, M. S. Carlino, J. L. SmithP. Mollee, M. Burgess, S. Mapp, C. Keane, V. Atkinson, S. A. Parikh, S. N. Markovic, W. Ding, T. G. Call, P. J. Hampel, G. V. Long, J. A. Wargo, A. Ferrajoli

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. Patients and methods: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. Results: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. Conclusions: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.

Original language	English (US)
Pages (from-to)	796-805
Number of pages	10
Journal	Annals of Oncology
Volume	34
Issue number	9
DOIs	https://doi.org/10.1016/j.annonc.2023.06.007
State	Published - Sep 2023

Keywords

anti-CTLA-4
anti-PD-1
chronic lymphoid leukemia
immune checkpoint inhibitors
melanoma

ASJC Scopus subject areas

Hematology
Oncology

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10.1016/j.annonc.2023.06.007

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Cass, S. H., Tobin, J. W. D., Seo, Y. D., Gener-Ricos, G., Keung, E. Z., Burton, E. M., Davies, M. A., McQuade, J. L., Lazar, A. J., Mason, R., Millward, M., Sandhu, S., Khoo, C., Warburton, L., Guerra, V., Haydon, A., Dearden, H., Menzies, A. M., Carlino, M. S., ... Ferrajoli, A. (2023). Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia. Annals of Oncology, 34(9), 796-805. https://doi.org/10.1016/j.annonc.2023.06.007

Cass, SH, Tobin, JWD, Seo, YD, Gener-Ricos, G, Keung, EZ, Burton, EM, Davies, MA , McQuade, JL , Lazar, AJ, Mason, R, Millward, M, Sandhu, S, Khoo, C, Warburton, L, Guerra, V, Haydon, A, Dearden, H, Menzies, AM, Carlino, MS, Smith, JL, Mollee, P, Burgess, M, Mapp, S, Keane, C, Atkinson, V, Parikh, SA, Markovic, SN, Ding, W, Call, TG, Hampel, PJ, Long, GV, Wargo, JA & Ferrajoli, A 2023, 'Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia', Annals of Oncology, vol. 34, no. 9, pp. 796-805. https://doi.org/10.1016/j.annonc.2023.06.007

@article{756d0135f48d4e3e96eeaaeeb4b9127e,

title = "Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia",

abstract = "Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. Patients and methods: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. Results: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. Conclusions: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.",

keywords = "anti-CTLA-4, anti-PD-1, chronic lymphoid leukemia, immune checkpoint inhibitors, melanoma",

author = "Cass, {S. H.} and Tobin, {J. W.D.} and Seo, {Y. D.} and G. Gener-Ricos and Keung, {E. Z.} and Burton, {E. M.} and Davies, {M. A.} and McQuade, {J. L.} and Lazar, {A. J.} and R. Mason and M. Millward and S. Sandhu and C. Khoo and L. Warburton and V. Guerra and A. Haydon and H. Dearden and Menzies, {A. M.} and Carlino, {M. S.} and Smith, {J. L.} and P. Mollee and M. Burgess and S. Mapp and C. Keane and V. Atkinson and Parikh, {S. A.} and Markovic, {S. N.} and W. Ding and Call, {T. G.} and Hampel, {P. J.} and Long, {G. V.} and Wargo, {J. A.} and A. Ferrajoli",

note = "Publisher Copyright: {\textcopyright} 2023 European Society for Medical Oncology",

year = "2023",

month = sep,

doi = "10.1016/j.annonc.2023.06.007",

language = "English (US)",

volume = "34",

pages = "796--805",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "9",

}

TY - JOUR

T1 - Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia

AU - Cass, S. H.

AU - Tobin, J. W.D.

AU - Seo, Y. D.

AU - Gener-Ricos, G.

AU - Keung, E. Z.

AU - Burton, E. M.

AU - Davies, M. A.

AU - McQuade, J. L.

AU - Lazar, A. J.

AU - Mason, R.

AU - Millward, M.

AU - Sandhu, S.

AU - Khoo, C.

AU - Warburton, L.

AU - Guerra, V.

AU - Haydon, A.

AU - Dearden, H.

AU - Menzies, A. M.

AU - Carlino, M. S.

AU - Smith, J. L.

AU - Mollee, P.

AU - Burgess, M.

AU - Mapp, S.

AU - Keane, C.

AU - Atkinson, V.

AU - Parikh, S. A.

AU - Markovic, S. N.

AU - Ding, W.

AU - Call, T. G.

AU - Hampel, P. J.

AU - Long, G. V.

AU - Wargo, J. A.

AU - Ferrajoli, A.

PY - 2023/9

Y1 - 2023/9

N2 - Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. Patients and methods: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. Results: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. Conclusions: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.

AB - Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. Patients and methods: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. Results: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. Conclusions: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.

KW - anti-CTLA-4

KW - anti-PD-1

KW - chronic lymphoid leukemia

KW - immune checkpoint inhibitors

KW - melanoma

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DO - 10.1016/j.annonc.2023.06.007

M3 - Article

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AN - SCOPUS:85167984912

SN - 0923-7534

VL - 34

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JO - Annals of Oncology

JF - Annals of Oncology

IS - 9

ER -

Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia

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